CASE REPORT |
https://doi.org/10.5005/jp-journals-10028-1663 |
Recurrence of Fever after Antitubercular Therapy: Think of Immune Reconstitution Inflammatory Syndrome—A Case Report
1–4Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India
Corresponding Author: Harpreet Singh, Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India, Phone: +91 8288025893, e-mail: hs.30.singh@gmail.com
Received: 02 August 2023; Accepted: 13 April 2024; Published on: 05 July 2024
ABSTRACT
Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is an uncommon phenomenon in an immunocompetent host. It may present in paradoxical and unmasking forms. In any patient with clinical deterioration after an initial response to antitubercular therapy, paradoxical reaction should be kept as an important differential after ruling out resistance to therapy. Here we present a young male with mediastinal and abdominal lymph node tuberculosis having TB-IRIS after 4 weeks of initiation of antitubercular therapy.
How to cite this article: Gulia M, Singh H, Suri V, et al. Recurrence of Fever after Antitubercular Therapy: Think of Immune Reconstitution Inflammatory Syndrome—A Case Report. J Postgrad Med Edu Res 2024;58(2):74–75.
Source of support: Nil
Conflict of interest: Dr Vikas Suri is associated as the National Editorial Board member of this journal and this manuscript was subjected to this journal’s standard review procedures, with this peer review handled independently of this editorial board member and his research group.
Patient consent statement: The author(s) have obtained written informed consent from the patient for publication of the case report details and related images.
Keywords: Antitubercular therapy, Case report, GeneXpert Mycobacterium tuberculosis, Nonsteroidal anti-inflammatory drugs, Tuberculosis-associated immune reconstitution inflammatory syndrome
INTRODUCTION
Tuberculosis (TB) is a major public health problem predominantly prevalent in developing nations. Early diagnosis and prompt treatment reduce transmission, morbidity, and mortality. Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is an abnormal, excessive immune response against dead or alive Mycobacterium tuberculosis (MTB). It may occur in either human immunodeficiency virus (HIV) infected patients or, rarely, in immunocompetent patients. The estimated frequency of TB-IRIS in different studies is around 2–23% in immunocompetent patients.1 TB-IRIS can be misdiagnosed as secondary infection, treatment failure, drug-resistant TB, or relapse; differentiating these entities is important as further treatment will differ. Here we report a case of an immunocompetent patient with extrapulmonary TB presenting with recurrence of symptoms and lymphadenopathy after an initial response with antituberculosis treatment.
CASE DESCRIPTION
An 18-year-old male was admitted with intermittent fever up to 102°F, with significant loss of appetite and loss of weight of around 8 kg over 6 months. Initial evaluation at a local hospital showed a positive Mantoux test but negative sputum GeneXpert for MTB and did not respond to antibiotics. He was started on weight-based antitubercular therapy with four drugs (isoniazid, rifampicin, pyrazinamide, and ethambutol in fixed drug combination). He remained afebrile for the next 4 weeks, but again developed intermittent fever up to 101°F, with no other localizing signs and symptoms. Laboratory investigations showed hemoglobin of 11.9 gm/dL, total leukocyte count of 13,000 × 109/L) and platelet count of 2,40,000/mm3. There was an elevation of ESR (erythrocyte sedimentation rate) of 76 mm in the 1 hour, qCRP (quantitative C-reactive protein) of 82 mg/L, and serum ferritin of 428 ng/mL. The rest of the fever work was negative. Contrast-enhanced computed tomography (CT) of the chest and abdomen done before presentation to us showed enlarged lymph nodes with peripheral enhancement in pretracheal, prevascular, peripancreatic, and periportal regions (Fig. 1A). Ultrasound-guided fine needle aspiration from the periportal lymph node showed necrotizing granulomatous inflammation with positive GeneXpert for MTB and indeterminant rifampicin sensitivity. A repeat CT of the chest and abdomen done in our hospital after 1 month of the first CT showed an increase in the size of lymph nodes in the superior mediastinum, perivascular, and pretracheal regions (Fig. 1B). A possibility of drug-resistant extrapulmonary TB vs TB-IRIS was kept. He was continued on four drugs along with the addition of oral levofloxacin and injection streptomycin. A repeat ultrasound-guided abdominal lymph node biopsy did not show any rifampicin resistance on GeneXpert-MTB testing. A diagnosis of TB-IRIS was made, and tablet naproxen 500 mg twice a day was started; he became afebrile after a week and was discharged with tapering of naproxen done over 3 weeks. He completed 9 months of antitubercular therapy with resolution of symptoms and reduction in the size of lymph nodes.
Figs 1A and B: (A) Contrast-enhanced CT of chest showing enlarged pretracheal and prevascular lymph nodes before presentation to our hospital (yellow arrow marks); (B) Contrast-enhanced CT of chest showing an increase in size of pretracheal and prevascular lymph nodes after the initiation of antitubercular therapy (yellow arrow marks)
DISCUSSION
Tuberculosis-associated immune reconstitution inflammatory syndrome is a dysregulated immune response against Mycobacterium in a patient on antitubercular treatment, clinically manifesting as paradoxical worsening of TB-related symptoms and/or recurrence of primary tuberculous lesions or the development of new lesions.1,2 Two types of TB-IRIS described are paradoxical form and unmasking, with paradoxical form being more common. Although these paradoxical reactions are more common in HIV–TB coinfection after antiretroviral therapy initiation, they may also occur in an immunocompetent host. The estimated incidence ranges from 8 to 36% in HIV patients vs 2.4% in immunocompetent individuals.3 Risk factors include young age, male gender, disseminated disease, CD4+ T-cell lymphopenia or the use of biological agents.4 The median time to onset of paradoxical response after initiation of ATT in an immunocompetent individual is around 21–58 days vs 14–28 days in HIV–TB coinfection.5 The all-cause mortality has been estimated at around 3%.6 Qualitative and quantitative immune reconstitution, especially T helper CD4+ immune response, high antigenic load, and host genetic susceptibility, has been implicated in the immunopathogenesis of IRIS.7 When antitubercular treatment is introduced, there is a reduction in mycobacterial load leading to reversal of cellular cytokine pattern, that is, immune reconstitution producing a paradoxical reaction. An exaggerated response may produce excessive immunopathological damage at the tissue level.
The most common site involved in an immunocompetent patient is extrapulmonary TB, with lymph nodes involvement in 68% and lungs in 16% of cases.4 Pulmonary manifestations include worsening/fresh infiltrates, pleural effusion, or endobronchial lesions. In about 25% of HIV-negative cases, there can be new lymphadenopathy or enlargement of existing nodes.1 Diagnostic criteria include4: (a) Initial clinical and radiological improvement after starting ATT; (b) paradoxical worsening in the form of recurrence of symptoms and/or radiological findings at primary site or at new locations during or after ATT completion; (c) exclusion of other likely causes of deterioration; (d) absence of situations associated with reduction in the efficacy of anti-TB drugs (e.g., poor compliance, drug malabsorption, drugs side effects).
There is no standard treatment protocol for TB-IRIS in immunocompetent cases, with the majority responding to nonsteroidal anti-inflammatory drugs and continuation of ATT. Complicated cases may warrant use of immunomodulators such as corticosteroids or infliximab. Studies have shown that steroids significantly reduce days of hospitalization and outpatient therapeutic procedures, more rapidly improving symptoms, quality-of-life score, and chest radiograph.8
ORCID
Manisha Gulia https://orcid.org/0000-0002-1828-1934
Harpreet Singh https://orcid.org/0000-0002-1308-7198
Vikas Suri https://orcid.org/0000-0001-6379-2744
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